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Microcantilever-based Nanomechanical Studies of the Orphan Nuclear Receptor Pregnane X Receptor-Ligand Interactions

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Author(s): Kasey L. Hill | Pampa Dutta | Zhou Long | Michael J. Sepaniak

Journal: Journal of Biomaterials and Nanobiotechnology
ISSN 2158-7027

Volume: 02;
Issue: 02;
Start page: 133;
Date: 2011;
Original page

Keywords: Microcantilevers | Nanobiosensing | Pregnane X receptor | Estrogen receptor | Endocrine disrupting chemicals | Bioarray

ABSTRACT
Human pregnane X receptor (PXR) is of vital importance in pharmaceutical and exogenous compound metabolism within the body. This provides strong motivation for investigating this orphan receptor’s activation by various pharmaceuticals, xenobiotics, and endocrine disrupting chemicals (EDCs). A nanomechanical transducer is developed to study xenobiotic and EDC interactions with the bioreceptor PXR’s ligand binding domain (LBD). The combination of immobilized LBD PXR with a nanostructured microcantilever (MC) platform allows for the sensitive, label-free study of ligand interaction with the receptor. PXR shows real-time, reversible responses when exposed to a specific pharmaceutical, EDCs, and xenobiotic ligands. Three EDCs binding interactions are tested, which include phthalic acid, nonylphenol, and bisphenol A, with PXR. PXR LBD was exposed to rifampicin, a potent PXR activator, with various injection and recovery times to study their interaction. A two protein array of PXR and estrogen receptor ? (ER-?) directly compares the nanomechanical responses of these receptors with rifampicin on a single platform.
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